Engineered biosynthesis of hybrid macrolide polyketides containing D-angolosamine and D-mycaminose moieties |
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Authors: | Schell Ursula Haydock Stephen F Kaja Andrew L Carletti Isabelle Lill Rachel E Read Eliot Sheehan Lesley S Low Lindsey Fernandez Maria-Jose Grolle Friederike McArthur Hamish A I Sheridan Rose M Leadlay Peter F Wilkinson Barrie Gaisser Sabine |
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Institution: | Biotica Technology Ltd, Chesterford Research Park, Little Chesterford, Saffron Walden, Essex, CB10 1XL, UK. |
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Abstract: | The glycosylation of natural product scaffolds with highly modified deoxysugars is often essential for their biological activity, being responsible for specific contacts to molecular targets and significantly affecting their pharmacokinetic properties. In order to provide tools for the targeted alteration of natural product glycosylation patterns, significant strides have been made to understand the biosynthesis of activated deoxysugars and their transfer. We report here efforts towards the production of plasmid-borne biosynthetic gene cassettes capable of producing TDP-activated forms of D-mycaminose, D-angolosamine and D-desosamine. We additionally describe the transfer of these deoxysugars to macrolide aglycones using the glycosyl transferases EryCIII, TylMII and AngMII, which display usefully broad substrate tolerance. |
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